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Perilipin 2 Improves Insulin Sensitivity in Skeletal Muscle Despite Elevated Intramuscular Lipid Levels
Type 2 diabetes is characterized by excessive lipid storage in skeletal muscle. Excessive intramyocellular lipid (IMCL) storage exceeds intracellular needs and induces lipotoxic events, ultimately contributing to the development of insulin resistance. Lipid droplet (LD)–coating proteins may control...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478528/ https://www.ncbi.nlm.nih.gov/pubmed/22807032 http://dx.doi.org/10.2337/db11-1402 |
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author | Bosma, Madeleen Hesselink, Matthijs K.C. Sparks, Lauren M. Timmers, Silvie Ferraz, Maria João Mattijssen, Frits van Beurden, Denis Schaart, Gert de Baets, Marc H. Verheyen, Fons K. Kersten, Sander Schrauwen, Patrick |
author_facet | Bosma, Madeleen Hesselink, Matthijs K.C. Sparks, Lauren M. Timmers, Silvie Ferraz, Maria João Mattijssen, Frits van Beurden, Denis Schaart, Gert de Baets, Marc H. Verheyen, Fons K. Kersten, Sander Schrauwen, Patrick |
author_sort | Bosma, Madeleen |
collection | PubMed |
description | Type 2 diabetes is characterized by excessive lipid storage in skeletal muscle. Excessive intramyocellular lipid (IMCL) storage exceeds intracellular needs and induces lipotoxic events, ultimately contributing to the development of insulin resistance. Lipid droplet (LD)–coating proteins may control proper lipid storage in skeletal muscle. Perilipin 2 (PLIN2/adipose differentiation–related protein [ADRP]) is one of the most abundantly expressed LD-coating proteins in skeletal muscle. Here we examined the role of PLIN2 in myocellular lipid handling and insulin sensitivity by investigating the effects of in vitro PLIN2 knockdown and in vitro and in vivo overexpression. PLIN2 knockdown decreased LD formation and triacylglycerol (TAG) storage, marginally increased fatty-acid (FA) oxidation, and increased incorporation of palmitate into diacylglycerols and phospholipids. PLIN2 overexpression in vitro increased intramyocellular TAG storage paralleled with improved insulin sensitivity. In vivo muscle-specific PLIN2 overexpression resulted in increased LD accumulation and blunted the high-fat diet–induced increase in protein content of the subunits of the oxidative phosphorylation (OXPHOS) chain. Diacylglycerol levels were unchanged, whereas ceramide levels were increased. Despite the increased IMCL accumulation, PLIN2 overexpression improved skeletal muscle insulin sensitivity. We conclude that PLIN2 is essential for lipid storage in skeletal muscle by enhancing the partitioning of excess FAs toward TAG storage in LDs, thereby blunting lipotoxicity-associated insulin resistance. |
format | Online Article Text |
id | pubmed-3478528 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-34785282013-11-01 Perilipin 2 Improves Insulin Sensitivity in Skeletal Muscle Despite Elevated Intramuscular Lipid Levels Bosma, Madeleen Hesselink, Matthijs K.C. Sparks, Lauren M. Timmers, Silvie Ferraz, Maria João Mattijssen, Frits van Beurden, Denis Schaart, Gert de Baets, Marc H. Verheyen, Fons K. Kersten, Sander Schrauwen, Patrick Diabetes Metabolism Type 2 diabetes is characterized by excessive lipid storage in skeletal muscle. Excessive intramyocellular lipid (IMCL) storage exceeds intracellular needs and induces lipotoxic events, ultimately contributing to the development of insulin resistance. Lipid droplet (LD)–coating proteins may control proper lipid storage in skeletal muscle. Perilipin 2 (PLIN2/adipose differentiation–related protein [ADRP]) is one of the most abundantly expressed LD-coating proteins in skeletal muscle. Here we examined the role of PLIN2 in myocellular lipid handling and insulin sensitivity by investigating the effects of in vitro PLIN2 knockdown and in vitro and in vivo overexpression. PLIN2 knockdown decreased LD formation and triacylglycerol (TAG) storage, marginally increased fatty-acid (FA) oxidation, and increased incorporation of palmitate into diacylglycerols and phospholipids. PLIN2 overexpression in vitro increased intramyocellular TAG storage paralleled with improved insulin sensitivity. In vivo muscle-specific PLIN2 overexpression resulted in increased LD accumulation and blunted the high-fat diet–induced increase in protein content of the subunits of the oxidative phosphorylation (OXPHOS) chain. Diacylglycerol levels were unchanged, whereas ceramide levels were increased. Despite the increased IMCL accumulation, PLIN2 overexpression improved skeletal muscle insulin sensitivity. We conclude that PLIN2 is essential for lipid storage in skeletal muscle by enhancing the partitioning of excess FAs toward TAG storage in LDs, thereby blunting lipotoxicity-associated insulin resistance. American Diabetes Association 2012-11 2012-10-16 /pmc/articles/PMC3478528/ /pubmed/22807032 http://dx.doi.org/10.2337/db11-1402 Text en © 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Metabolism Bosma, Madeleen Hesselink, Matthijs K.C. Sparks, Lauren M. Timmers, Silvie Ferraz, Maria João Mattijssen, Frits van Beurden, Denis Schaart, Gert de Baets, Marc H. Verheyen, Fons K. Kersten, Sander Schrauwen, Patrick Perilipin 2 Improves Insulin Sensitivity in Skeletal Muscle Despite Elevated Intramuscular Lipid Levels |
title | Perilipin 2 Improves Insulin Sensitivity in Skeletal Muscle Despite Elevated Intramuscular Lipid Levels |
title_full | Perilipin 2 Improves Insulin Sensitivity in Skeletal Muscle Despite Elevated Intramuscular Lipid Levels |
title_fullStr | Perilipin 2 Improves Insulin Sensitivity in Skeletal Muscle Despite Elevated Intramuscular Lipid Levels |
title_full_unstemmed | Perilipin 2 Improves Insulin Sensitivity in Skeletal Muscle Despite Elevated Intramuscular Lipid Levels |
title_short | Perilipin 2 Improves Insulin Sensitivity in Skeletal Muscle Despite Elevated Intramuscular Lipid Levels |
title_sort | perilipin 2 improves insulin sensitivity in skeletal muscle despite elevated intramuscular lipid levels |
topic | Metabolism |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478528/ https://www.ncbi.nlm.nih.gov/pubmed/22807032 http://dx.doi.org/10.2337/db11-1402 |
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